Ptosis, and Falls

High match MYASTHENIC SYNDROME, CONGENITAL, 13; CMS13

Congenital myasthenic syndrome-13 is an autosomal recessive neuromuscular disorder characterized by onset of proximal muscle weakness in the first decade. EMG classically shows a decremental response to repeated nerve stimulation. Affected individuals show a favorable response to acetylcholinesterase (AChE) inhibitors (summary by Belaya et al., 2012).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

MYASTHENIC SYNDROME, CONGENITAL, 13; CMS13 Is also known as myasthenic syndrome, congenital, with tubular aggregates 2|cmsta2

• Generalized hypotonia
• Scoliosis
• Muscle weakness
• Ptosis
• Motor delay

SOURCES: OMIM MENDELIAN

High match 6-PYRUVOYL-TETRAHYDROPTERIN SYNTHASE DEFICIENCY

6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is one of the causes of malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency. Not only does tetrahydrobiopterin deficiency cause hyperphenylalaninemia, it is also responsible for defective neurotransmission of monoamines because of malfunctioning tyrosine and tryptophan hydroxylases, both tetrahydrobiopterin-dependent hydroxylases.

6-PYRUVOYL-TETRAHYDROPTERIN SYNTHASE DEFICIENCY Is also known as hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Muscular hypotonia

SOURCES: ORPHANET MENDELIAN

High match PSYCHOMOTOR REGRESSION-OCULOMOTOR APRAXIA-MOVEMENT DISORDER-NEPHROPATHY SYNDROME

PSYCHOMOTOR REGRESSION-OCULOMOTOR APRAXIA-MOVEMENT DISORDER-NEPHROPATHY SYNDROME Is also known as cerebrorenal syndrome, perez type

• Intellectual disability
• Generalized hypotonia
• Ataxia
• Strabismus
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

High match TUBULAR AGGREGATE MYOPATHY

• Intellectual disability
• Muscle weakness
• Ptosis
• Flexion contracture
• Visual impairment

SOURCES: OMIM ORPHANET MENDELIAN

High match MYOPATHY, TUBULAR AGGREGATE, 1; TAM1

Tubular aggregates in muscle, first described by Engel (1964), are structures of variable appearance consisting of an outer tubule containing either one or more microtubule-like structures or amorphous material. They are a nonspecific pathologic finding that may occur in a variety of circumstances, including alcohol- and drug-induced myopathies, exercise-induced cramps or muscle weakness, and inherited myopathies. Tubular aggregates are derived from the sarcoplasmic reticulum (Salviati et al., 1985) and are believed to represent an adaptive mechanism aimed at regulating an increased intracellular level of calcium in order to prevent the muscle fibers from hypercontraction and necrosis (Martin et al., 1997; Muller et al., 2001). Genetic Heterogeneity of Tubular Aggregate MyopathySee also TAM2 (OMIM ), caused by mutation in the ORAI1 gene (OMIM ) on chromosome 12q24.

MYOPATHY, TUBULAR AGGREGATE, 1; TAM1 Is also known as tubular aggregate myopathy|myopathy, tubular aggregate|tam

• Muscle weakness
• Ptosis
• Flexion contracture
• Dysarthria
• Fatigue

SOURCES: OMIM MENDELIAN

High match VERVERI-BRADY SYNDROME; VERBRAS

Ververi-Brady syndrome is a disorder characterized by mild developmental delay, mild intellectual disability and speech delay, and mild dysmorphic facial features. Affected individuals can usually attend mainstream schools with support, and may also show autistic features (summary by Ververi et al., 2018).

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Growth delay

SOURCES: OMIM MENDELIAN

High match MYASTHENIC SYNDROME, CONGENITAL, 11, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS11

Congenital myasthenic syndrome associated with AChR deficiency is a disorder of the postsynaptic neuromuscular junction (NMJ) clinically characterized by early-onset muscle weakness with variable severity. Electrophysiologic studies show low amplitude of the miniature endplate potential (MEPP) and current (MEPC) resulting from deficiency of AChR at the endplate. Treatment with cholinesterase inhibitors or amifampridine may be helpful (summary by Engel et al., 2015).For a discussion of genetic heterogeneity of CMS, see CMS1A (OMIM ).

MYASTHENIC SYNDROME, CONGENITAL, 11, ASSOCIATED WITH ACETYLCHOLINE RECEPTOR DEFICIENCY; CMS11 Is also known as cms1e, formerly|myasthenic syndrome, congenital, ie, formerly|cms ie, formerly

• Generalized hypotonia
• Hypertelorism
• Micrognathia
• Muscle weakness
• Ptosis

SOURCES: MESH OMIM MENDELIAN

High match LENNOX-GASTAUT SYNDROME

Lennox-Gastaut syndrome (LGS) belongs to the group of severe childhood epileptic encephalopathies.

• Intellectual disability
• Seizures
• Global developmental delay
• Ptosis
• Low-set ears

SOURCES: OMIM ORPHANET MENDELIAN

High match MYOPATHY, MYOFIBRILLAR, 8; MFM8

Myofibrillar myopathy-8 is an autosomal recessive myopathy characterized by childhood onset of slowly progressive proximal muscle weakness and atrophy resulting in increased falls, gait problems, and difficulty running or climbing stairs. Upper and lower limbs are affected, and some individuals develop distal muscle weakness and atrophy. Ambulation is generally preserved, and patients do not have significant respiratory compromise. Muscle biopsy shows a mix of myopathic features, including myofibrillar inclusions and sarcomeric disorganization (summary by O'Grady et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy, see MFM1 (OMIM ).

• Generalized hypotonia
• Scoliosis
• Micrognathia
• Muscle weakness
• Ptosis

SOURCES: OMIM MENDELIAN

High match KLIPPEL-FEIL ANOMALY-MYOPATHY-FACIAL DYSMORPHISM SYNDROME

Klippel-Feil syndrome-4 with nemaline myopathy and facial dysmorphism is an autosomal recessive disorder characterized mainly by severe hypotonia apparent from infancy. Klippel-Feil anomaly is primarily defined by fusion of the cervical spine, with associated low posterior hairline and limited neck mobility being observed in about half of patients (summary by Alazami et al., 2015).For a general description and a discussion of genetic heterogeneity of Klippel-Feil syndrome, see KFS1 (OMIM ).

• Short stature
• Generalized hypotonia
• Microcephaly
• Scoliosis
• Micrognathia

SOURCES: OMIM ORPHANET MENDELIAN